Coarse-grained molecular dynamics simulation of transport through the nuclear pore complex

This thesis is devoted to disclose the mechanism of nucleo-cytoplasmic transport by using coarse-grained molecular dynamics simulations of disordered proteins in nuclear pore complex (NPC). NPCs are highly selective gates which control all the transportations across nuclear envelope. The coarse-grained model is used to address several questions regarding the role of the disordered FG-Nups in nucleo-cytoplasmic transport. Our results show that the distribution of the FG-Nups forms a specific pattern inside the pore consisting of a low density region at the center of the pore surrounded by a high density region more towards the scaffold of the NPC, which is rich in FG-repeats. Furthermore, our analysis suggests that the specific doughnut-like distribution of the FG-Nups inside the pore is a characteristic footprint of viable NPCs and is encoded in the amino acid sequence of the FG-Nups. Studying the energetics of transport for model cargoes shows that the probability of transport decreases as the size of the cargo exceeds 4.7 nm. However, the energy barrier of the NPC can be lowered by adding binding spots on the surface of the cargo.